Metastability of Cell Migration Polarity

细胞迁移极性的亚稳定性

• 批准号: 1133476
• 负责人: Jason Haugh
• 金额: $ 34万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1133476&HistoricalAwards=false
• 关键词: Metastability; Cell; Migration; Polarity

The overall goal of the proposed project is to elucidate the fundamental physical mechanisms governing the reorientation of cell migration polarity, which affects how persistently the cells maintain their directionality of movement and their ability to follow spatial cues during physiological processes such as wound healing, the immune response, and embryonic development. The phosphoinositide 3-kinase (PI3K) signaling pathway has been implicated in the control of cell reorientation, which is achieved by stabilizing the branching of existing cell protrusions activity. Using an approach integrating live-cell fluorescence microscopy, image analysis, and computational modeling, the team will characterize and manipulate the dynamics of signal transduction pathways, focal adhesions, and the actin cytoskeleton during protrusion branching. The hallmarks of cell reorientation thusly identified will be re-evaluated in PI3K-inhibited cells to evaluate if the dynamics are altered and how. These research objectives are to be integrated with educational activities, and, through the support and training of graduate students and the participation of undergraduate students, the project will contribute to the training of researchers in the cross-disciplinary areas of engineering analysis and cell biology.

该项目的总体目标是阐明控制细胞迁移极性重新定向的基本物理机制，这会影响细胞在生理过程中（如伤口愈合，免疫反应和胚胎发育）如何持续保持其运动方向性及其遵循空间线索的能力。 磷脂酰肌醇3-激酶（PI 3 K）信号传导通路参与了细胞重定向的控制，这是通过稳定现有细胞突起活性的分支来实现的。 使用集成活细胞荧光显微镜，图像分析和计算建模的方法，该团队将表征和操纵信号转导途径，粘着斑和肌动蛋白细胞骨架在突起分支过程中的动态。 将在PI 3 K抑制的细胞中重新评价由此鉴定的细胞重定向的标志，以评价动力学是否改变以及如何改变。 这些研究目标将与教育活动相结合，通过对研究生的支持和培训以及本科生的参与，该项目将有助于培养工程分析和细胞生物学跨学科领域的研究人员。